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意大利无临床明显传染性肝病人群隐匿性 HCV 感染的流行率和随访情况。

Prevalence and follow-up of occult HCV infection in an Italian population free of clinically detectable infectious liver disease.

机构信息

Unit of Cancer Epidemiology, C.E.R.M.S., University of Turin, Turin, Italy.

出版信息

PLoS One. 2012;7(8):e43541. doi: 10.1371/journal.pone.0043541. Epub 2012 Aug 22.

Abstract

BACKGROUND

Occult hepatitis C virus infection (OCI) is a recently described phenomenon characterized by undetectable levels of HCV-RNA in serum/plasma by current laboratory assays, with identifiable levels in peripheral blood mononuclear cells (PBMCs) and/or liver tissue by molecular tests with enhanced sensitivity. Previous results from our group showed an OCI prevalence of 3.3% in a population unselected for hepatic disease. The present study aimed to evaluate OCI prevalence in a larger cohort of infectious liver disease-free (ILDF) subjects. Clinical follow-up of OCI subjects was performed to investigate the natural history of the infection.

METHODS AND FINDINGS

439 subjects referred to a Turin Blood Bank for phlebotomy therapy were recruited. They included 314 ILDF subjects, 40 HCV-positive subjects and 85 HBV-positive subjects, of whom 7 were active HBV carriers. Six subjects (4/314 ILDF subjects [1.27%] and 2/7 active HBV carriers [28%]) were positive for HCV-RNA in PBMCs, but negative for serological and virological markers of HCV, indicating OCI. HCV genotypes were determined in the PBMCs of 3/6 OCI subjects two had type 1b; the other had type 2a/2c. OCI subjects were followed up for at least 2 years. After 12 months only one OCI persisted, showing a low HCV viral load (3.73×10(1) UI/ml). By the end of follow-up all OCI subjects were negative for HCV. No seroconversion, alteration of liver enzyme levels, or reduction of liver synthesis occurred during follow-up.

CONCLUSIONS

This study demonstrated the existence of OCI in ILDF subjects, and suggested a high OCI prevalence among active HBV carriers. Follow-up suggested that OCI could be transient, with a trend toward the decrease of HCV viral load to levels undetectable by conventional methods after 12-18 months. Confirmation studies with a longer follow-up period are needed for identification of the OCI clearance or recurrence rates, and to characterize the viruses involved.

摘要

背景

隐匿性丙型肝炎病毒感染(OCI)是一种最近描述的现象,其特点是当前实验室检测方法无法检测到血清/血浆中的 HCV-RNA,但分子检测方法具有更高的灵敏度,可在周围血单核细胞(PBMC)和/或肝组织中检测到可识别的水平。我们小组之前的结果显示,在未经选择的肝脏疾病人群中,OCI 的患病率为 3.3%。本研究旨在评估更大的无传染性肝病(ILDF)受试者队列中 OCI 的患病率。对 OCI 受试者进行临床随访,以研究感染的自然史。

方法和发现

招募了 439 名因采血治疗而前往都灵血液银行的受试者。其中包括 314 名无传染性肝病(ILDF)受试者、40 名 HCV 阳性受试者和 85 名 HBV 阳性受试者,其中 7 名是活跃的 HBV 携带者。6 名受试者(4/314 名 ILDF 受试者[1.27%]和 2/7 名活跃的 HBV 携带者[28%])在 PBMC 中检测到 HCV-RNA 阳性,但 HCV 的血清学和病毒学标志物均为阴性,表明存在 OCI。在 3/6 名 OCI 受试者的 PBMC 中确定了 HCV 基因型,其中 2 名患有 1b 型;另一名患有 2a/2c 型。对 OCI 受试者进行了至少 2 年的随访。12 个月后,只有一名 OCI 持续存在,且 HCV 病毒载量较低(3.73×101 UI/ml)。随访结束时,所有 OCI 受试者均对 HCV 呈阴性。在随访期间,未发生 HCV 血清转换、肝酶水平改变或肝脏合成减少。

结论

本研究证明了 OCI 在无传染性肝病(ILDF)受试者中的存在,并提示活跃的 HBV 携带者中存在较高的 OCI 患病率。随访表明,OCI 可能是短暂的,在 12-18 个月后,HCV 病毒载量呈下降趋势,降至常规方法无法检测的水平。需要进行具有更长随访期的确认研究,以确定 OCI 的清除或复发率,并对涉及的病毒进行特征描述。

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